These studies will explore treatment strategies for chronic Lyme disease and will be conducted at two centers, New England Medical Center/Tufts University School of Medicine and Westchester County Medical Center affiliated with New York Medical College. The coordinating center, and the central laboratory facility will be at New England Medical Center. Investigators will perform an initial assessment of each patient for collection of demographic data, a history of exposure to ticks in geographic regions with endemic B. burgdorferi infection, clinical manifestations of acute Lyme disease, clinical manifestations of chronic Lyme disease, and prior treatment. History and physical examination will include evaluation of tender points, detailed neurologic examination and neuropsychological testing. Subjects will receive intravenous therapy at home consisting of ceftriaxone at a dose of 2 grams daily or intravenous placebo (dextrose) for the first 30 days of the treatment period followed by doxycycline 100 mg bid orally (or placebo) for 60 consecutive days. Patients will be measured at baseline, three months (at the end of treatment) and at six months. Due to the absence of specific markers for chronic Lyme disease, outcomes will be assessed based upon measurement of the subject's physical and neuropsychological well being. The primary outcome for this study is defined as an improvement in the patients' health-related quality of life (HQL). Health-related quality of life will be measured using the SF-36 Health Survey.